Aeterna Zentaris said today it is assessing the future of its registrational adult growth hormone deficiency (AGHD) treatment MacrilenTM (macimorelin) after receiving a Complete Response Letter from the FDA.
The FDA told Aeterna Zentaris its NDA for Macrilen cannot be approved in its present form. The agency cited concerns about data from the company’s Phase III pivotal trial of the drug candidate, the company added.
“Following the FDA's decision, we are currently reviewing the outstanding issues stated in the CRL in order to evaluate our options and future plans for Macrilen,” David Dodd, Aeterna Zentaris’ chairman and CEO, said in a statement.
Macrilen is an orally-active ghrelin agonist designed to stimulate the secretion of growth hormone. The compound has been granted orphan drug designation by the FDA for AGHD.
In its Complete Response Letter, the FDA said the planned analysis of the pivotal trial did not meet its stated primary efficacy objective as agreed to in a Special Protocol Assessment agreement between the company and the agency.
The letter also cited issues related to what it said was the lack of complete and verifiable source data for determining whether patients were accurately diagnosed with AGHD.
“In light of the failed primary analysis and data deficiencies noted, the clinical trial does not by itself support the indication,” the FDA stated in its letter, according to Aeterna Zentaris.
To address the deficiencies it identified, the FDA added, Aeterna Zentaris will need to demonstrate the efficacy of macimorelin as a diagnostic test for growth hormone deficiency in a new, confirmatory clinical study.
The letter also outlined that a serious event of electrocardiogram QT interval prolongation occurred, for which attribution to drug could not be excluded. Therefore a dedicated thorough QT study to evaluate the effect of macimorelin on the QT interval would be necessary.
The FDA complete response letter marks Aeterna Zentaris’ latest setback over the past nearly two years. In June, the company disclosed plans to slice its workforce to 65 staffers from the 90 it employed at the start of 2014—part of a “resources optimization program” that Dodd said was intended to “streamline our operations, optimize our resources and R&D productivity, reduce our operating cash burn and more appropriately, align our financial resources with our strategic goal of transitioning into a commercially operating specialty biopharmaceutical company.”
Last year, Aeterna Zentaris halted a Phase III trial that assessed perifosine in combination with bortezomib (Velcade®) and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma. The company cited the recommendation of the study’s independent data safety monitoring board, which concluded it was highly unlikely the study would achieve a significant difference in its primary endpoint, progression free survival. According to the company, no safety concerns were raised.